P1065: UPDATED RESULTS FROM AN OPEN-LABEL PHASE 1/2 STUDY OF FAVEZELIMAB IN COMBINATION WITH PEMBROLIZUMAB IN PATIENTS WITH ANTI–PD-1–NAIVE RELAPSED OR REFRACTORY CLASSICAL HODGKIN LYMPHOMA
Authors: Nathalie Johnson, David Lavie, Peter Borchmann, Gareth Gregory, Alex F. Herrera, Leonard Minuk, Vladan Vucinic, Philippe Armand, Abraham Avigdor, Robin Gasiorowski, Yair Herishanu, Colm Keane, John Kuruvilla, Rachel Marceau West, Pallavi Pillai, Patricia Marinello, John Timmerman
Journal: HemaSphere (2023)

Topic: 17. Hodgkin lymphoma - Clinical Background: Programmed death 1 (PD-1) inhibitors play a key role in treating relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL), but improved treatment response remains an important clinical objective. Lymphocyte-activation gene 3 (LAG-3) downregulates T-cell activity and is commonly coexpressed with PD-1 on anergic T cells. Dual PD-1 and LAG-3 blockade has demonstrated antitumor activity, leading to FDA approval for unresectable or metastatic melanoma. Favezelimab (anti–LAG-3) is being investigated in combination with pembrolizumab (anti–PD-1) in a multicohort phase 1/2 efficacy and safety study (NCT03598608) in patients with R/R hematologic malignancies. Initial results demonstrated that pembrolizumab 200 mg and favezelimab 800 mg Q3W exhibited promising antitumor activity and acceptable safety in anti–PD-1–naive patients with R/R cHL (cohort 1; Johnson NA et al. J Clin Oncol. 2022;40(16 suppl):7516). Aims: Evaluate efficacy and safety of favezelimab + pembrolizumab in anti-PD-1–naive patients with R/R cHL. Methods: Part 1 was the safety lead-in phase to determine the recommended phase 2 dose (RP2D) followed by a dose-expansion phase (part 2). Patients in cohort 1 had R/R cHL after autologous stem cell transplantation (ASCT) (or were ineligible for ASCT), or did not respond to salvage chemotherapy, and had no prior anti–PD-1 therapy. Part 1 included patients from all cohorts who received pembrolizumab 200 mg IV Q3W and favezelimab at a starting dose of 200 mg, escalating to 800 mg IV Q3W using a modified toxicity probability interval method. In part 2, patients received pembrolizumab 200 mg Q3W plus favezelimab at the established RP2D (800 mg Q3W) for ≤35 cycles (~2 years). Primary end points were safety and RP2D. Objective response rate (ORR) was a secondary end point. Duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were exploratory. Results: Thirty patients were enrolled in cohort 1. Median age was 40.5 years, 53% had an ECOG PS of 0, and 80% had ≤3 prior lines of therapy. At data cutoff (August 31, 2022), 10 patients (33%) had completed 2 years of study treatment, 14 patients (47%) had discontinued (9 progressive disease; 4 adverse events; 1 nonadherence to study drug regimen), and 6 (20%) had treatment ongoing. After a 25.5-month median follow-up (first dose to data cutoff; range, 18.0-37.2), 24 patients had objective response (ORR, 80% [95% CI, 61-92]; 10 [33%] complete responses, 14 [47%] partial responses). 29 patients (97%) had reduction in target lesion size from baseline and 25 (83%) had ≥50% reduction from baseline. Median DOR was 25.6 months (range, 0.0+ to 28.8+); an estimated 54% of responders remained in response ≥15 months. Median PFS was 19.4 months (95% CI, 9.0-28.5); 15-month PFS rate was 53%. Median OS was not reached (95% CI, NR-NR); 15-month OS rate was 93%. Among 26 patients (87%) with treatment related AEs, most common (≥15%) were hypothyroidism (27%); infusion-related reaction (23%); fatigue (20%); pruritus and headache (17% each). Grade 3/4 treatment related AEs occurred in 7 patients (23%). No deaths were treatment related. Of 3 patients who received hematopoietic stem cell transplantation after completion of study treatment, 1 had a grade 3/4 AE unrelated to study treatment (increased blood bilirubin) that resolved. Summary/Conclusion: Favezelimab + pembrolizumab continued to demonstrate sustained antitumor activity and acceptable safety in anti–PD-1–naive patients with R/R cHL. Further studies comparing this combination with pembrolizumab alone would be beneficial. Keywords: Clinical trial, Hodgkin’s lymphoma, Immunotherapy